Staphylococcus aureus causes diseases chiefly through the production of virulence factors such as hemolysins, enterotoxins and toxic shock syndrome toxin. The synthesis of virulence factors in S. aureus is controlled by a regulatory RNA molecule, RNAIII (Novick, et al., EMBO J. 12, 3967 (1993), Balaban et al., FEMS Microbiol. Letts. 133, 155 (1995), Moerfeldt et al., EMBO J. 14, 4569 (1995)), encoded by the agr locus. The rnaiii gene of the agr locus is transcribed in culture only from the midexponential phase of growth, and is autoinduced by the protein RNAIII activating protein (RAP)(Balaban et al., Proc. Natl. Acad. Sci. U.S.A. 92, 1619 (1995)). RAP is continuously secreted by the bacteria and only activates RNAIII at a concentration threshold (ibid).
Antibodies to RAP block the activation of rnaiii in vitro. A peptide, termed RNAIII inhibiting peptide (RIP) is produced by a nonpathogenic strain of S. aureus mutated by nitrosoguanidine (ibid). RIP competes with RAP for the activation of RNAIII, and thus inhibits toxin production by S. aureus (ibid).
Staphylococcus aureus causes diseases ranging from minor skin infections to life-threatening deep infections such as pneumonia, endocarditis, meningitis, post-operative wound infections, septicemia, and toxic shock syndrome (Silverstein et al., in Microbiology, Davis et al., eds. (Lippincott, Philadelphia, 1990), pp. 485-506). Hospitalized patients are at particular risk, with over 500,000 nosocomial infections per year (Panlilio, et al., Inf. Contr. and Hosp. Epidem. 13, 582 (1992)). The emergence of drug resistance has made many of the available antimicrobial agents ineffective. Therefore, alternative methods for the prevention and treatment of bacterial infections in general and S. aureus infections in particular are eagerly sought. The instant invention addresses this need and others.